DNA cleavage by oxygen radicals produced in the absence of metal ions or light

Nagai, Katsuyuki; Carter, Barbara J.; Xu, Jianming; Hecht, Sidney M.

doi:10.1021/ja00013a077

Cited by 56 publications

(27 citation statements)

References 1 publication

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“…Related studies of relevance include DNA cleavage by phenazine di-N-oxides such as (30) (reducing agent: dithiothreitol; aerobic) [159], voltammetric investigations of phenazine and quinoxaline N-oxides and the relationships between redox properties and antimicrobial activity [105,107], and reduction of rezasurin (31) [160,161]. A full discussion is precluded here, but damage in aerobic systems probably arises through redox cycling (superoxide formation) and trace metal catalysis of Fenton chemistry.…”

Section: Reactions Of Activated Quinone Drugsmentioning

confidence: 99%

Electron Transfer and Oxidative Stress as Key Factors in the Design of Drugs Selectively Active in Hypoxia.

Wardman

2001

CMC

140

110

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Hypoxia is a feature of some regions of many tumours, ischaemic events, and arthritis. Drugs activated in hypoxia have wide potential application, particularly in overcoming the resistance of hypoxic tumour cells to radiotherapy. Key features of such drugs include redox properties appropriate for activation by reductase enzymes (typically flavoproteins), and oxygen-sensitive reduction chemistry such that normal levels of oxygen inhibit or reverse reduction. In many cases this selectivity is achieved by a fast, free-radical reaction in which the drug radical (often an obligate intermediate in drug reduction) reduces oxygen to form superoxide radicals and thus 'futile cycles' the drug in normoxic tissues. However, this enhances cellular oxidative stress, which may be linked to normal tissue toxicity. Appropriate redox properties are found with nitroarene, quinone, or aromatic N-oxide moieties. A particularly promising and versatile exploitation of bioreductive activation is for reduction of such 'triggers' to activate release of an 'effector', an agent that can obviously be active against diverse conditions associated with hypoxia. The same approach can also be used in diagnosis of hypoxia. Much information concerning the reactions of intermediates in drug action and the quantitative prediction of redox properties of analogues has been accrued. Drug design can be mechanism-led, with the wealth of literature quantifying redox properties of drug candidates a rich source of potential new leads. There is a clear appreciation of the kinetic factors that limit drug efficacy or selectivity. Thus the potential for rapid expansion of these concepts to diverse diseases is considerable.

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Section: Reactions Of Activated Quinone Drugsmentioning

confidence: 99%

Electron Transfer and Oxidative Stress as Key Factors in the Design of Drugs Selectively Active in Hypoxia.

Wardman

2001

CMC

140

110

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“…However, the effects of dissolved gases on such interactions have traditionally not take into account. This is strange, because the existing hypotheses imply such an impact, in [22,23]. Implying such an impact, we found the following relationship (table 2), in [24].…”

Section: The Influence Dissolved Gases On the Interactionmentioning

confidence: 82%

Nucleic Acids in Atypical Conditions

Pivovarenko¹

2015

EJB

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Abstract:Here we describe some properties of nucleic acids, which observed in 'atypical" experiments. So, we show that physical and chemical properties of nucleic acids depend on dissolved gases. We show particularly that thermal hyperchromism of DNA depends on dissolved oxygen and (or) air. It has been showed most importantly the thermal hyperchromism does not observe for DNA degassed solutions. Here we also demonstrate the difference between some chemical properties of nucleic acids in degassed solutions and in solutions saturated with hydrogen or oxygen. We illustrate too the difference between physical and chemical properties of nucleic acids in the homogenous and gradient-containing solutions; the last case we offer as approximation of the conditions, in which the nucleic acids exist in vivo.

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“…Additionally, resorcinolic lipids are effective functional inhibitors of triglyceride synthesis and the enzymatic oxidation of unsaturated fatty acids [65,66], which makes possible a synergistic effect of those compounds on the organisms into which they were introduced. Recent reports indicating the participation of resorcinolic lipids in DNA damage [67][68][69][70][71] and inhibition of its repair [72,73] with parallel enhancement of anticancer drugs activity, strongly support the necessity for further studies of this interesting group of natural compounds. The concominant biological activities may be a key issue in creating a kind of universal vesicular systems based on natural and biodegradable modifiers.…”

Section: A Novel Approach To Liposomal Anthracycline Drugs: Plarosomesmentioning

confidence: 92%

Liposomal drug delivery, a novel approach: PLARosomes.

Kozubek¹,

Gubernator²,

Przeworska³

et al. 2000

Acta Biochim Pol

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Almost from the time of their rediscovery in the 60's and the demonstration of their entrapment potential, liposomal vesicles have drawn attention of researchers as potential carriers of various bioactive molecules that could be used for therapeutic applications in humans and animals. Several commercial liposome-based drugs have already been discovered, registered and introduced with great success on the pharmaceutical market. However, further studies, focusing on the elaboration of more efficient and stable amphiphile-based vesicular (or non-viral) drug carriers are still under investigation. In this review we present the achievements of our group in this field. We have discovered that natural amphiphilic dihydroxyphenols and their semisynthetic derivatives are promising additives to liposomal lipid compositions. The presence of these compounds in lipid composition enhances liposomal drug encapsulation, reduces the amount of the lipid carrier necessary for efficient entrapment of anthracycline drugs by a factor of two, stabilizes liposomal formulation of the drug (both in suspension and in a lyophilized powder), does not influence liposomal fate in the blood circulation system and benefits from other biological activities of their resorcinolic lipid modifiers.

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DNA cleavage by oxygen radicals produced in the absence of metal ions or light

Cited by 56 publications

References 1 publication

Electron Transfer and Oxidative Stress as Key Factors in the Design of Drugs Selectively Active in Hypoxia.

Electron Transfer and Oxidative Stress as Key Factors in the Design of Drugs Selectively Active in Hypoxia.

Nucleic Acids in Atypical Conditions

Liposomal drug delivery, a novel approach: PLARosomes.

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